The TAM receptor tyrosine kinase family member AXL plays critical roles in tissue homeostasis, survival, chemoresistance, and motility. This study investigates the receptor expression in six AML cell lines and bone marrow myeloblasts from 25 patients with myeloid neoplasms. We found that AXL expression was generally absent or very low in AML myeloblasts.
View Article and Find Full Text PDFBackground Aims: Vγ9Vδ2 T cells are under investigation as alternative effector cells for adoptive cell therapy (ACT) in cancer. Despite promising in vitro results, anti-tumor efficacies in early clinical studies have been lower than expected, which could be ascribed to the complex interplay of tumor and immune cell metabolism competing for the same nutrients in the tumor microenvironment.
Methods: To contribute to the scarce knowledge regarding gamma delta T-cell metabolism, we investigated the metabolic phenotype of 25-day-expanded Vγ9Vδ2 T cells and how it is intertwined with functionality.
Myeloproliferative neoplasms (MPN) are chronic cancers of the hematopoietic stem cells in the bone marrow, and patients often harbor elevated numbers of circulating platelets (PLT). We investigated the frequencies of circulating PLT-lymphocyte aggregates in MPN patients and the effect of PLT-binding on CD8 T cell function. The phenotype of these aggregates was evaluated in 50 MPN patients and 24 controls, using flow cytometry.
View Article and Find Full Text PDFThere is an increasing interest in the development of Receptor Tyrosine Kinases inhibitors (RTKIs) for cancer treatment, as dysregulation of RTK expression can govern oncogenesis. Among the newer generations of RTKIs, many target Mer Tyrosine Kinase (MERTK) and Fms related RTK 3 (FLT3). Next to being overexpressed in many cancers, MERTK and FLT3 have important roles in immune cell development and function.
View Article and Find Full Text PDFThe human Vγ9Vδ2 T cell is a unique cell type that holds great potential in immunotherapy of cancer. In particular, the therapeutic potential of this cell type in adoptive cell therapy (ACT) has gained interest. In this regard optimization of expansion methods and functional characterization is desirable.
View Article and Find Full Text PDFTyro3, Axl and MerTK (TAM) receptors are receptor tyrosine kinases which play important roles in efferocytosis and in the balancing of immune responses and inflammation. TAM receptor activation is induced upon binding of the ligands protein S (Pros1) or growth arrest-specific protein 6 (Gas6) which act as bridging molecules for binding of phosphatidyl serine (PtdSer) exposed on apoptotic cell membranes. Upon clearance of apoptotic cell material, TAM receptor activation on innate cells suppresses proinflammatory functions, thereby ensuring the immunologically silent removal of apoptotic material in the absence of deleterious immune responses.
View Article and Find Full Text PDFHuman Vγ9Vδ2 T cells are a unique T-cell type, and data from recent studies of Vγ9Vδ2 T cells emphasize their potential relevance to cancer immunotherapy. Vγ9Vδ2 T cells exhibit dual properties since they are both antigen-presenting cells and cytotoxic toward cancer cells. The majority of Vγ9Vδ2 T cells are double-negative for the co-receptors CD4 and CD8, and only 20-30% express CD8.
View Article and Find Full Text PDFCancer immunotherapy has shown great advances during recent years, but it has yet to reach its full potential in all cancer types. Adoptive cell therapy (ACT) is now an approved treatment option for certain hematological cancers and has also shown success for some solid cancers. Still, benefit and eligibility do not extend to all patients.
View Article and Find Full Text PDF